MicroRNA-200c-3p/ZEB2 loop plays a crucial role in the tumor progression of prostate carcinoma

Abstract

Background: The microRNA (miRNA) miR-200c-3p is involved in the tumorigenesis and progression of a variety of cancers. However, the underlying regulatory role of miR-200c-3p in prostate cancer (PCa) remains unclear. Methods: Online databases including Oncomine, Linkedomics and StarBase were used to investigate the clinical significance of miR-200c-3p, along with associated gene targets. PCa tissues and adjacent normal tissues were used for the detection of miR-200c-3p expression. A lentivirus overexpressing miR-200c-3p was constructed and transfected into PC3 and DU145 cells. Cell formation of proliferation, migration, and invasion were determined by cell viability and colony-formation assay, wound healing assay, and Matrigel invasion assay, respectively. Epithelial-mesenchymal transition (EMT)-associated markers were determined by qRT-PCR and Western blot. A luciferase reporter assay was performed to determine the direct relationship of miR-200c-3p and ZEB2. The tumor-suppressive role of miR-200c-3p was further confirmed by a xenograft tumor model and immunohistochemical (IHC) staining. Results: Online database analyses showed that miR-200c-3p was associated with pathologic T and N stage in PCa, and miR-200c-3p was downregulated in PCa tissues. Overexpression of miR-200c-3p was considered a tumor suppressor and was found to significantly suppress the formation of migration and invasion in PCa cells via repression of E-cadherin-induced EMT. The bioinformatic database indicated that ZEB2 has a significant correlation with miR-200c-3p and was upregulated in PCa tissues. Further, ZEB2 expression was suppressed by the upregulation of miR-200c-3p and was identified as a direct target of miR-200c-3p. In addition, repression of ZEB2 could restore the levels of miR-200c-3p in PCa cells in turn, suggesting a potential negative loop between miR-200c-3p and ZEB2. miR-200c-3p also had an antitumor effect by negatively regulating ZEB2 in a xenograft mouse model. Conclusions: Taken together, the results of our study demonstrated the novel regulatory loop of miR-200c-3/ZEB2 in PCa progression, providing effective therapeutic strategies for PCa in the future.

Hypoxia‐inhibited miR‐338‐3p suppresses breast cancer progression by directly targeting ZEB2

“…Physiologically, ZEB2, a zinc finger homeodomain, functions as a molecular master switch during the EMT process that occurs in tumor aggression, including BC 27‐29 . Recently, ZEB2 has gained attention for its pro‐oncogenic functions: overexpression of ZEB2 contributes to the degree of malignancy, rapid cell proliferation, and poor patient survival in different tumors, and knockdown of ZEB2 expression inhibits cell proliferation, migration, and invasion 28,30,31 . Based on biomedical databases query and previous reports, 10,32 we confirmed that miR‐338‐3p could directly bind to ZEB2 3’UTR, as evidenced by dual‐luciferase reporter assay and Western blot assay.…”

MiR-629-3p-induced downregulation of SFTPC promotes cell proliferation and predicts poor survival in lung adenocarcinoma

“…Two online tools, including Target scan [34] and TACCO [35], were used to screen for candidate microRNAs probably targeting SFTPC mRNA to suppress its protein expression. StarBase was utilized to predict the association between miR-629-3p expression and SFTPC expression in LUAD [36].…”

miR-637 Prevents Glioblastoma Progression by Interrupting ZEB2/WNT/β-catenin Cascades

“…hindered liver cancer malignant behavior via inactivation of WNT/β-catenin pathways (Zhang et al 2019c). Zhang and colleagues proved that the ZEB2/miR-200c loop participated in prostate carcinoma progression (Zhang et al 2019a). We found crosstalk between ZEB2 and canonical WNT/β-catenin pathways, which are frequently activated in GBM progression, providing attractive therapeutic targets against GBM.…”